Subjects With Relapsed or Refractory Multiple Myeloma MedDRA version: 12.1 Level: LLT Classification code 10028228 Term: Multiple myeloma
Conditions
Interventions
Product Name: CNTO328
Product Code: CNTO328
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Siltuximab
Current Sponsor code: CNTO328
Other descriptive name: Chimeric murine
Sponsors
Janssen Biologics B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Potential subjects must satisfy all of the following criteria to be enrolled in the study: • = 18 years of age • Confirmed diagnosis of multiple myeloma requiring treatment • Measurable secretory disease, defined as either serum M-protein = 1 g/dL or urine M-protein (light chain) = 200 mg/24 hours • Must have received 1 to 3 lines of prior treatment for multiple myeloma (a single line of treatment may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy) • Must have achieved a response (MR or better) to at least 1 prior line of treatment • Must have progressed on (including relapse from CR) or be refractory (defined as 11.5 mg/dL [2.8 mmol/L]) due to multiple myeloma • Subjects must not be refractory to any previous line of treatment that included a proteasome inhibitor • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 • Clinical laboratory test values meeting the following criteria: o Hemoglobin = 8 g/dL(= 4.96 mmol/L) without transfusion support within 7 days before the laboratory test o Absolute neutrophil count (ANC) = 1.0 x 109/L o Platelet count = 50 x 109/L without transfusion support within 7 days before the laboratory test o AST = 2.5 x ULN o ALT = 2.5 x ULN o Total bilirubin = x ULN o Calculated creatinine clearance = 20 mL/min o Corrected serum calcium =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Potential subjects who meet any of the following criteria will be excluded from participating in the study: o Diagnosis of primary amyloidosis, plasma cell leukemia, or other conditions in which a paraprotein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions o Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 o Allogeneic bone marrow transplantation within 28 days before the first dose of study agent. Subjects for whom bone marrow transplant is planned within 12 months after study start are also ineligible. o Chemotherapy or radiation therapy within 21 days before the first dose of study agent (42 days for nitrosoureas) o Clinically significant infection, including known HIV or hepatitis C infection, or known hepatitis B surface antigen positivity o Major surgery including open biopsy (excluding bone marrow) within 21 days before study treatment or planning to have surgery (except for minor surgical procedures) during the study (kyphoplasty is not considered major surgery) o Previous or concurrent malignancies other than multiple myeloma, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer from which the subject has been disease-free for = 3 years o Concurrent medical condition (eg, acute pulmonary infiltrative disease, autoimmune disease, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in the study. This includes subjects who the investigator believes would not tolerate starting doses of VELCADE or dexamethasone. o Significant cardiac disease characterized by significant ischemic coronary disease, significant arrhythmias, or congestive heart failure (NYHA Class III or IV) or myocardial infarction within 6 months before the first dose of study agent o Vaccination with live attenuated vaccines within 4 weeks of the first administration of study agent o Known, unmanageable severe infusion related reactions to monoclonal antibodies or to murine, chimeric, or human proteins or their excipients o Prior exposure to agents targeting IL-6 or the IL-6 receptor o Received any investigational agent (including vaccines) within 30 days before the first dose of study agent o Pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine if there is an improvement in progression-free survival (PFS) when siltuximab is added to VELCADE® (bortezomib) and dexamethasone in subjects with relapsed or refractory multiple myeloma.;Secondary Objective: The secondary objectives of this study are to assess safety, additional measures of clinical benefit, patient-reported outcomes (PROs), pharmacokinetics of dexamethasone and siltuximab, antibodies to siltuximab (immunogenicity), exploratory biomarkers, and health economic outcomes.;Primary end point(s): The study will end at the time of the final analysis, which will be after 280 deaths have been recorded. This is expected to occur approximately 5 years after the first subject starts study treatment. Subjects who are benefiting from treatment (complete response [CR] or partial response [PR]) at the end of study may be eligible to receive siltuximab in a separate protocol. | — |
Countries
Belgium, Czech Republic, Germany, Italy, Netherlands, Portugal, Spain, United Kingdom
Outcome results
None listed